Molecular linkage between the kinase ATM and NF-κB signaling in response to genotoxic stimuli (Publication with Expression of Concern. See vol. 371, pg. 1002, 2021)

The transcription factor NF-kappa B modulates apoptotic responses induced by genotoxic stress. We show that NF-kappa B essential modulator (NEMO), the regulatory subunit of I kappa B kinase (IKK) (which phosphorylates the NF-kappa B inhibitor I kappa B), associates with activated ataxia telangiectasia mutated (ATM) after the induction of DNA double-strand breaks. ATM phosphorylates serine-85 of NEMO to promote its ubiquitin-dependent nuclear export. ATM is also exported in a NEMO-dependent manner to the cytoplasm, where it associates with and causes the activation of IKK in a manner dependent on another IKK regulator, a protein rich in glutamate, leucine, lysine, and serine (ELKS). Thus, regulated nuclear shuttling of NEMO links two signaling kinases, ATM and IKK, to activate NF-kappa B by genotoxic signals.